Photoactivation switch from type II to type I reactions by electron-rich micelles for improved photodynamic therapy of cancer cells under hypoxia

Abstract

Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble in water. Many new nanoplatforms have been successfully established to improve the delivery efficiency of PS drugs. However, few reported studies have investigated how the carrier microenvironment may affect the photophysical properties of PS drugs and subsequently, their biological efficacy in killing malignant cells. In this study, we describe the modulation of type I and II photoactivation processes of the photosensitizer, 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment. Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles increased photoactivations from type II to type I mechanisms, which significantly increased the generation of O2•− through the electron transfer pathway over 1O2 production through energy transfer process. The PDPA micelles led to enhanced phototoxicity over the electron-deficient poly(D,L-lactide) control in multiple cancer cell lines under argon-saturated conditions. These data suggest that micelle carriers may not only improve the bioavailability of photosensitizer drugs, but also modulate photophysical properties for improved PDT efficacy.

Clinical use of photodynamic therapy in ocular tumors

“…In a Type I reaction, it transfers its energy into oxygen, forming superoxide radicals, while in a Type II reaction, singlet oxygen is formed. 56 Both of these reactions are oxygen dependent, and several studies have confirmed in vivo oxygen depletion during PDT with direct measurements. 200 The therapeutic efficacy of PDT is shown to be greater when tumor oxygenation during PDT is conserved as it results in more tumor damage, a better immune response, longer stabilization, and increased cures.…”

“…Singlet oxygen is the primary cytotoxic agent responsible for photobiological activity in PDT; however, Type I reactions may also play a role. 56 There are three important mechanisms of action in PDT: 1) the direct cytotoxic effect, 2) the destruction of peritumoral vasculature, and 3) the local inflammatory reaction resulting in increased autophagy. 130 Singlet oxygen can directly kill tumor cells through the induction of necrosis and/or apoptosis, and can cause the destruction of tumor vasculature.…”

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…1) (Dolmans et al 2003). It is often difficult to establish how much each of these processes contributes to the overall cell damage, but it is generally accepted that the singlet oxygen is the most important factor in the targeted killing of tumour cells in sufficiently oxygenated tumours, whereas the type I process is more important in hypoxic conditions (Sibata et al 2000;Ding et al 2011). In addition to the direct ROS-mediated damage, two additional mechanisms contribute to tumour cell elimination: vascular damage and induction of immune responses.…”

Photodynamic Action of Single-Walled Carbon Nanotubes

“…A few studies have suggested that it depends on the structure and concentration of the PS and the concentration of O 2 . [24][25][26] The effects of PDT on tumor tissues are now known to be due to four mechanisms: (1) direct cytotoxicity, (2) vascular injury, (3) inflammatory response, and (4) host immune response 27,28) (Fig. 5).…”